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Radiological evaluation of newly diagnosed non-brainstem pediatric high-grade glioma in the HERBY phase II trial


Daniel Rodriguez

Chris Jones

Pascale Varlet

Alan Mackay

Daniel Warren

Monika Warmuth-Metz


Raphael Calmon

Darren Hargrave


Maura Massimino

Le Deley

Frank Saran

Raphael F Rousseau

Gudrun Zahlmann

Amedeo A Azizi

Josep Garcia

Gilles Vassal

Jacques Grill

Paul S Morgan

Tim Jaspan


Purpose: The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathologic and molecular data.

Experimental Design: Radiological, pathologic, and molecular data were correlated with trial clinical information to retrospectively re-evaluate event-free survival (EFS) and overall survival (OS).

Results: One-hundred thirteen patients were randomized to the RT/TMZ arm (n = 54) or the RT/TMZ+BEV (BEV arm; n = 59). The tumor arose in the cerebral hemispheres in 68 patients (Cerebral group) and a midline location in 45 cases (Midline group). Pathologic diagnosis was available in all cases and molecular data in 86 of 113. H3 K27M histone mutations were present in 23 of 32 Midline cases and H3 G34R/V mutations in 7 of 54 Cerebral cases. Total/near-total resection occurred in 44 of 68 (65%) Cerebral cases but in only 5 of 45 (11%) Midline cases (P < 0.05). Leptomeningeal metastases (27 cases, 13 with subependymal spread) at relapse were more frequent in Midline (17/45) than in Cerebral tumors (10/68, P < 0.05). Mean OS (14.1 months) and EFS (9.0 months) in Midline tumors were significantly lower than mean OS (20.7 months) and EFS (14.9 months) in Cerebral tumors (P < 0.05). Pseudoprogression occurred in 8 of 111 (6.2%) cases.

Conclusions: This study has shown that the poor outcome of midline tumors (compared with cerebral) may be related to (1) lesser surgical resection, (2) H3 K27M histone mutations, and (3) higher leptomeningeal dissemination.


Rodriguez, D., Jones, C., Varlet, P., Mackay, A., Warren, D., Warmuth-Metz, M., …Jaspan, T. (2020). Radiological evaluation of newly diagnosed non-brainstem pediatric high-grade glioma in the HERBY phase II trial. Clinical Cancer Research, 26(8), 1856-1865.

Journal Article Type Article
Acceptance Date Dec 13, 2019
Online Publication Date Jan 10, 2020
Publication Date 2020-04
Deposit Date Jan 8, 2020
Publicly Available Date Jan 11, 2021
Journal Clinical Cancer Research
Print ISSN 1078-0432
Electronic ISSN 1557-3265
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 26
Issue 8
Pages 1856-1865
Keywords Cancer Research; Oncology
Public URL


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